Using Wearable Sensors and Machine Learning to Assess Upper Limb Function in Huntington's Disease.

Huntington's disease (HD), like many other neurological disorders, affects both lower and upper limb function that is typically assessed in the clinic - providing a snapshot of disease symptoms. Wearable sensors enable the collection of real-world data that can complement such clinical assessments and provide a more comprehensive insight into disease symptoms. In this context, almost all studies are focused on assessing lower limb function via monitoring of gait, physical activity and ambulation. In this study, we monitor upper limb function during activities of daily living in individuals with HD (n = 16), prodromal HD (pHD, n = 7), and controls (CTR, n = 16) using a wrist-worn wearable sensor, called PAMSys ULM, over seven days. The participants were highly compliant in wearing the sensor with an average daily compliance of 99% (100% for HD, 98% for pHD, and 99% for CTR). Goal-directed movements (GDM) of the hand were detected using a deep learning model, and kinematic features of each GDM were estimated. The collected data was used to predict disease groups (i.e., HD, pHD, and CTR) and clinical scores using a combination of statistical and machine learning-based models. Significant differences in GDM features were observed between the groups. HD participants performed fewer GDMs with long duration (> 7.5 seconds) compared to CTR (p-val = 0.021, d = -0.86). In velocity and acceleration metrics, the highest effect size feature was the entropy of the velocity zero-crossing length segments (HD vs CTR p-val <0.001, d = -1.67; HD vs pHD p-val = 0.043, d=-0.98; CTR vs pHD p-val = 0.046, d=0.96). In addition, this same variable showed a strongest correlation with clinical scores. Classification models achieved good performance in distinguishing HD, pHD and CTR individuals with a balanced accuracy of 67% and a 0.72 recall for the HD group, while regression models accurately predicted clinical scores. Notably the explained variance for the upper extremity function subdomain scale of Unified Huntington's Disease Rating Scale (UHDRS) was the highest, with the model capturing 60% of the variance. Our findings suggest the potential of wearables and machine learning for early identification of phenoconversion, remote monitoring in HD, and evaluating new treatments efficacy in clinical trials and medicine.

Enhancing Histopathological Image Classification Performance through Synthetic Data Generation with Generative Adversarial Networks.

Breast cancer is the second most common cancer worldwide, primarily affecting women, while histopathological image analysis is one of the possibile methods used to determine tumor malignancy. Regarding image analysis, the application of deep learning has become increasingly prevalent in recent years. However, a significant issue is the unbalanced nature of available datasets, with some classes having more images than others, which may impact the performance of the models due to poorer generalizability. A possible strategy to avoid this problem is downsampling the class with the most images to create a balanced dataset. Nevertheless, this approach is not recommended for small datasets as it can lead to poor model performance. Instead, techniques such as data augmentation are traditionally used to address this issue. These techniques apply simple transformations such as translation or rotation to the images to increase variability in the dataset. Another possibility is using generative adversarial networks (GANs), which can generate images from a relatively small training set. This work aims to enhance model performance in classifying histopathological images by applying data augmentation using GANs instead of traditional techniques.

The prohibition of recreational hunting of wild ungulates in Spanish National Parks: Challenges and opportunities.

A new regulation has led to the prohibition of recreational hunting on estates located within Spanish National Parks (NPs). Before the ban, eleven NPs in Spain had already reported negative ecological consequences associated with high densities of wild ungulates. The new situation that has occurred after the ban signifies that policies with which to control populations of wild ungulates in NPs, most of which do not have a sufficient natural capacity to regulate populations, depend exclusively on the parks' authorities. The banning of recreational hunting implies a series of social, ecological, economic and logistic challenges. The control of wild ungulate populations in NPs requires: i) the legal basis for culling; ii) social acceptance as regards removing animals and the extractive procedures employed in NPs; iii) the long-term monitoring of wild ungulates and the damages that they cause, and iv) sufficient financial and human resources. A more integrated management and policy plan is, therefore, required, which should be supported by two pillars: i) the sustainability of natural resources and the conservation of functional environments, and ii) providing society with explanations regarding the need to manage wild ungulates. In order to bridge the potential gap between these key pillars, it is important to involve stakeholders in the decision-making processes concerning wild ungulate management. The forthcoming changes in Spanish NPs provide a promising opportunity to make a substantial improvement to wild ungulate management in these protected areas. This management approach could, moreover, serve as an example and be transferred to other protected spaces.

Remote at-home wearable-based gait assessments in Progressive Supranuclear Palsy compared to Parkinson's Disease.

BACKGROUND: Wearable sensors can differentiate Progressive Supranuclear Palsy (PSP) from Parkinson's Disease (PD) in laboratory settings but have not been tested in remote settings. OBJECTIVES: To compare gait and balance in PSP and PD remotely using wearable-based assessments. METHODS: Participants with probable PSP or probable/clinically established PD with reliable caregivers, still able to ambulate 10 feet unassisted, were recruited, enrolled, and consented remotely and instructed by video conference to operate a study-specific tablet solution (BioDigit Home ™) and to wear three inertial sensors (LEGSys™, BioSensics LLC, Newton, MA USA) while performing the Timed Up and Go, 5 × sit-to-stand, and 2-min walk tests. PSPRS and MDS-UPDRS scores were collected virtually or during routine clinical visits. RESULTS: Between November, 2021- November, 2022, 27 participants were screened of whom 3 were excluded because of technological difficulties. Eleven PSP and 12 PD participants enrolled, of whom 10 from each group had complete analyzable data. Demographics were well-matched (PSP mean age = 67.6 ± 1.3 years, 40% female; PD mean age = 70.3 ± 1.8 years, 40% female) while disease duration was significantly shorter in PSP (PSP 14 ± 3.5 months vs PD 87.9 ± 16.9 months). Gait parameters showed significant group differences with effect sizes ranging from d = 1.0 to 2.27. Gait speed was significantly slower in PSP: 0.45 ± 0.06 m/s vs. 0.79 ± 0.06 m/s in PD (d = 1.78, p < 0.001). CONCLUSION: Our study demonstrates the feasibility of measuring gait in PSP and PD remotely using wearable sensors. The study provides insight into digital biomarkers for both neurodegenerative diseases. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04753320, first posted Febuary 15, 2021.

Utilizing speech analysis to differentiate progressive supranuclear palsy from Parkinson's disease.

INTRODUCTION: Distinguishing Parkinson's disease (PD) from Progressive supranuclear palsy (PSP) at early disease stages is important for clinical trial enrollment and clinical care/prognostication. METHODS: We recruited 21 participants with PSP(n = 11) or PD(n = 10) with reliable caregivers. Standardized passage reading, counting, and sustained phonation were recorded on the BioDigit Home tablet (BioSensics LLC, Newton, MA USA), and speech features from the assessments were analyzed using the BioDigit Speech platform (BioSensics LLC, Newton, MA USA). An independent t-test was performed to compare each speech feature between PSP and PD participants. We also performed Spearman's correlations to evaluate associations between speech measures and clinical scores (e.g., PSP rating scales and MoCA). In addition, the model's performance in classifying PSP and PD was evaluated using Rainbow passage reading analysis. RESULTS: During Rainbow passage reading, PSP participants had a significantly slower articulation rate (2.45(0.49) vs 3.60(0.47) words/minute), lower speech-to-pause ratio (2.33(1.08) vs 3.67(1.18)), intelligibility dynamic time warping (DTW, 0.26(0.19) vs 0.53(0.26)), and similarity DTW (0.43(0.27) vs 0.67(0.13)) compared to PD participants. PSP participants also had longer pause times (17.24(5.47) vs 8.45(3.13) sec) and longer total signal times (52.44(6.67) vs (36.67(6.73) sec) when reading the passage. In terms of the phonation 'a', PSP participants showed a significant higher spectral entropy, spectral centroid, and spectral spread compared to PD participants and no differences were found for phonation 'e'. PD participants had more accurate reverse number counts than PSP participants (14.89(3.86) vs 7.36(4.67)). PSP Rating Scale (PSPRS) dysarthria (r = 0.79, p = 0.004) and bulbar item scores (r = 0.803, p = 0.005) were positively correlated with articulation rate in reverse number counts. Correct reverse number counts were positively correlated with total Montreal Cognitive Assessment scores (r = 0.703, p = 0.016). Machine learning models using passage reading-derived measures obtained an AUC of 0.93, and the sensitivity/specificity in correctly classifying PSP and PD participants were 0.95 and 0.90, respectively. CONCLUSION: Our study demonstrates the feasibility of differentiating PSP from PD using a digital health technology platform. Further multi-center studies are needed to expand and validate our initial findings.

A Risk Assessment Tool for Predicting Fragility Fractures in People with HIV: Derivation and Internal Validation of the FRESIA Model.

People with HIV have a higher risk of fracture than the general population. Because of the low performance of the existing prediction tools, there is controversy surrounding fracture risk estimation in this population. The aim of the study was to develop a model for predicting the long-term risk of fragility fractures in people with HIV. We included 11,899 individuals aged ≥30 years from the Spanish HIV/AIDS research network cohort. We identified incident fragility fractures from medical records, defined as nontraumatic or those occurring after a casual fall, at major osteoporotic sites (hip, clinical spine, forearm, proximal humerus). Our model accounted for the competing risk of death and included 12 candidate predictors to estimate the time to first fragility fracture. We assessed the discrimination and calibration of the model and compared it with the FRAX tool. The incidence rate of fragility fractures was 4.34 (95% CI 3.61 to 5.22) per 1000 person-years. The final prediction model included age, chronic kidney disease, and chronic obstructive pulmonary disease as significant predictors. The model accurately predicted the 5- and 10-year risk of fragility fractures, with an area under the receiving operator characteristic curve of 0.768 (95% CI 0.722 to 0.814) and agreement between the observed and expected probabilities. Furthermore, it demonstrated better discrimination and calibration than the FRAX tool, improving the classification of over 35% of individuals with fragility fractures compared to FRAX. Our prediction model demonstrated accuracy in predicting the long-term risk of fragility fractures. It can assist in making personalized intervention decisions for individuals with HIV and could potentially replace the current tools recommended for fracture risk assessment in this population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

mRNA-based SARS-CoV-2 Comirnaty vaccine elicits weak and short specific memory B cell response in individuals with no previous infection.

Objectives: The dynamics of the memory B cell (MBC) repertoire after SARS-CoV-2 vaccination is crucial for assessing long-term immunity. We compare spike-specific MBC responses between SARS-CoV-2 unexposed and recovered individuals, and their impact on breakthrough infections during follow-up. Methods: Spike-specific MBC and T cells were quantified at inclusion and after two doses of mRNA vaccine in a longitudinal cohort of 85 naïve and 64 recovered participants (47 with positive serology and 17 with negative serology after infection). Results: At inclusion, there was minimal spike-specific MBC in naïve SARS-CoV-2 individuals. After the second vaccine dose, MBCs were significantly boosted in naïve individuals, but reached a significantly lower level than that observed even in unvaccinated SARS-CoV-2 convalescents (p<0.001). Furthermore, while the secondary memory B cell (MBC) population consisted of 100%, 33%, and 76% IgG+, IgM+, and IgA+ expressing cells, respectively, in the unexposed group, the MBC response showed a significant decrease across all isotypes. Similarly, although secondary specific IgG+, IgM+, and IgA+-MBC isotypes were found in 100%, 39%, and 76% of the unexposed participants, respectively, the magnitude of the MBC levels was significantly lower for all the isotypes compared to convalescents. Interestingly, convalescents without an initial serological response had a lower MBC response, like what found in unexposed subjects. There was an inverse correlation between specific MBCs (r=-0.307; p=0.027), especially for isotype IgA+ (r=-0.279, p=0.045), and the time since the second vaccination dose. Furthermore, during a median follow-up of 434 days (IQR, 339-495), 49 out of 149 individuals (33%) became infected, 29 in naïve and 20 in convalescent individuals, showing a significant correlation between spike-specific MBC magnitude after vaccination and the time for SARS-CoV-2 infection, especially for IgA+/IgG+ MBC isotypes. Conclusions: MBCs were primed by mRNA-based vaccination in most cases, but SARS-CoV-2 naïve individuals had a blunted specific MBC response, and this was associated with a shorter time to breakthrough SARS-CoV-2 infection.

Discordant Humoral and T-Cell Response to mRNA SARS-CoV-2 Vaccine and the Risk of Breakthrough Infections in Women with Breast Cancer, Receiving Cyclin-Dependent Kinase 4 and 6 Inhibitors.

Few data are available about the immune response to mRNA SARS-CoV-2 vaccines in patients with breast cancer receiving cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). We conducted a prospective, single-center study of patients with breast cancer treated with CDK4/6i who received mRNA-1273 vaccination, as well as a comparative group of healthcare workers. The primary endpoint was to compare the rate and magnitude of humoral and T-cell response after full vaccination. A better neutralizing antibody and anti-S IgG level was observed after vaccination in the subgroup of women receiving CDK4/6i, but a trend toward a reduced CD4 and CD8 T-cell response in the CDK4/6i group was not statistically significant. There were no differences in the rate of COVID-19 after vaccination (19% vs. 12%), but breakthrough infections were observed in those with lower levels of anti-S IgG and neutralizing antibodies after the first dose. A lower rate of CD4 T-cell response was also found in those individuals with breakthrough infections, although a non-significant and similar level of CD8 T-cell response was also observed, regardless of breakthrough infections. The rate of adverse events was higher in patients treated with CDK4/6i, without serious adverse events. In conclusion, there was a robust humoral response, but a blunted T-cell response to mRNA vaccine in women receiving CDK4/6i, suggesting a reduced trend of the adaptative immune response.

Coronary Artery Plaque Composition and Severity Relate to the Inflammasome in People With Treated Human Immunodeficiency Virus.

Background: Inflammasome activation is increased in people with human immunodeficiency virus (PWH), but its relationship with coronary plaque is poorly understood in this setting. Methods: In a large human immunodeficiency virus cardiovascular prevention cohort, relationships between caspase-1, interleukin (IL)-1ß, and IL-18 and coronary plaque indices were assessed by multivariate logistic regression. Results: Higher IL-18 and IL-1ß were associated with Leaman score, an integrative measure of plaque burden and composition. Conclusions: As Leaman score >5 is associated with cardiovascular events in the general population, future work is needed to determine how the inflammasome relates to events and whether strategies to reduce its activation affect events or plaque progression among PWH.

Impact of Previous Common Human Coronavirus Exposure on SARS-CoV-2-Specific T-Cell and Memory B-Cell Response after mRNA-Based Vaccination.

OBJECTIVE: T-cell responses against SARS-CoV-2 are observed in unexposed individuals, attributed to previous common human coronavirus (HCoV) infections. We evaluated the evolution of this T-cell cross-reactive response and the specific memory B-cells (MBCs) after the SARS-CoV-2 mRNA-based vaccination and its impact on incident SARS-CoV-2 infections. METHODS: This was a longitudinal study of 149 healthcare workers (HCWs) that included 85 unexposed individuals that were subdivided according to previous T-cell cross-reactivity, who were compared to 64 convalescent HCWs. Changes in specific T-cell response and memory B-cell (MBC) levels were compared at baseline and after two doses of the SARS-CoV-2 mRNA-based vaccine. RESULTS: A cross-reactive T-cell response was found in 59% of unexposed individuals before vaccination. Antibodies against HKU1 positively correlated with OC43 and 229E antibodies. Spike-specific MBCs was scarce in unexposed HCWs regardless of the presence of baseline T-cell cross-reactivity. After vaccination, 92% and 96% of unexposed HCWs with cross-reactive T-cells had CD4+ and CD8+ T-cell responses to the spike protein, respectively. Similar results to that were found in convalescents (83% and 92%, respectively). Contrarily, higher than that which was observed in unexposed individuals without T-cell cross-reactivity showed lower CD4+ and CD8+ T-cell responses (73% in both cases, p = 0.03). Nevertheless, previous cross-reactive T-cell response was not associated with higher levels of MBCs after vaccination in unexposed HCWs. During a follow-up of 434 days (IQR, 339-495) after vaccination, 49 HCWs (33%) became infected, with a significant positive correlation between spike-specific MBC levels and isotypes IgG+ and IgA+ after vaccination and a longer time to get infected. Interestingly, T-cell cross-reactivity did not reduce the time to vaccine breakthrough infections. CONCLUSION: While pre-existing T-cell cross-reactivity enhances the T-cell response after vaccination, it does not increase SARS-CoV-2-specific MBC levels in the absence of previous infection. Overall, the level of specific MBCs determines the time to breakthrough infections, regardless of the presence of T-cell cross-reactivity.

Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV.

BACKGROUND: Mechanisms contributing to COVID-19 severity in people with HIV (PWH) are poorly understood. We evaluated temporal changes in plasma proteins following SARS-CoV-2 infection and identified pre-infection proteomic markers associated with future COVID-19. METHODS: We leveraged data from the global Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). Antiretroviral therapy (ART)-treated PWH with clinical, antibody-confirmed COVID-19 as of September 2021 were matched on geographic region, age, and sample timing to antibody negative controls. For cases and controls, pre COVID-19 pandemic specimens were obtained prior to January 2020 to assess change over time and relationship to COVID-19 severity, using false-discovery adjusted mixed effects modeling. FINDINGS: We compared 257 unique plasma proteins in 94 COVID-19 antibody-confirmed clinical cases and 113 matched antibody-negative controls, excluding COVID-19 vaccinated participants (age 50 years, 73% male). 40% of cases were characterized as mild; 60% moderate to severe. Median time from COVID-19 infection to follow-up sampling was 4 months. Temporal patterns of protein changes differed based on COVID-19 disease severity. Among those experiencing moderate to severe disease vs. controls, NOS3 increased whereas ANG, CASP-8, CD5, GZMH, GZMB, ITGB2, and KLRD1 decreased. Higher pre-pandemic levels of granzymes A, B and H (GZMA, GZMB and GZMH) were associated with the future development of moderate-severe COVID-19 and were related to immune function. INTERPRETATION: We identified temporal changes in proteins closely linked to inflammatory, immune, and fibrotic pathways which may relate to COVID-19-related morbidity among ART-treated PWH. Further we identified key granzyme proteins associated with future COVID-19 in PWH. FUNDING: This study is supported through NIH grants U01HL123336, U01HL123336-06 and 3U01HL12336-06S3, to the clinical coordinating center, and U01HL123339, to the data coordinating center as well as funding from Kowa Pharmaceuticals, Gilead Sciences, and a grant award through ViiV Healthcare. The NIAID supported this study through grants UM1 AI068636, which supports the AIDS Clinical Trials Group (ACTG) Leadership and Operations Center, and UM1 AI106701, which supports the ACTG Laboratory Center. This work was also supported by NIAID through grant K24AI157882 to MZ. The work of IS was supported by the intramural research program of NIAID/NIH.

Lower T cell response against SARS-CoV-2 variants of concern after mRNA vaccine and risk of breakthrough infections in people with HIV.

OBJECTIVES: We evaluated T-cell immune responses against SARS-CoV-2 variants of concern (VOC) after vaccination in people with HIV (PWH), and their impact on the incidence of disease. METHODS: A prospective cohort study. Peripheral blood mononuclear cells (PBMCs) were collected a median of 53 days after second dose of mRNA vaccine. Humoral response and T cell responses against the spike (S) glycoprotein of wild-type SARS-CoV-2 (ancestral Wuhan variant) and mutated S-protein regions found in the Delta and Omicron variants were assessed by flow cytometry analysis. RESULTS: In 142 PWH without preceding SARS-CoV-2 infection, bivariate correlations showed a close association between T-cell responses to the different variants. However, despite at least 70% of PWH having a cellular immune response to any variant, CD4 + and CD8 + T cell responses against VOC were lower in frequency and magnitude (-3% and -20% for Delta, -33% and -28% for Omicron variant) compared with that observed against the Wuhan strain. A higher magnitude of SARS-CoV-2 spike-specific CD8 + T cell responses against all the variants was observed in those PWH with greater immune reconstitution. Notably, 27 symptomatic breakthrough infections (19%) in the setting of Delta and Omicron transmission were observed during follow-up, associated with a significant lower humoral and T-cell response to ancestral strain and VOC. On the contrary, only one PWH with COVID-19 (4%) required hospitalization. CONCLUSION: A blunted T-cell response against Delta and Omicron variant is observed in PWH who received two doses of mRNA vaccine. This lower immune response is associated with breakthrough SARS-CoV-2 infections.

Improving Recognition of Fracture Risk in People with Human Immunodeficiency Virus: Performance and Model Contribution of Two Common Risk Assessment Tools.

Current guidelines recommend screening people with HIV (PWH) for bone disease using predictive tools developed for the general population, although data on PWH are scarce. In this study, we assessed the performance of FRAX and QFracture scoring systems to predict the occurrence of fragility fractures in a prospective cohort of 17,671 adults with human immunodeficiency virus (HIV) included in the HIV/AIDS research network (CoRIS) in Spain. The survival estimates of fragility fractures during follow-up were calculated and FRAX and QFracture scores were computed at cohort inclusion. For both tools, discriminatory measures and the observed-to-expected (O/E) ratios were assessed. During a follow-up time of 42,411.55 person-years, 113 fragility fractures were recorded. Areas under the curve were 0.66 [95% confidence interval (95% CI) 0.61-0.71] for FRAX and 0.67 (95% CI 0.62-0.73) for QFracture for major osteoporotic fractures, and 0.72 (95% CI 0.57-0.88) and 0.81 (95% CI 0.68-0.95) for hip fracture, respectively. The O/E was 1.67 for FRAX and 5.49 for QFracture for major osteoporotic fractures, and 11.23 for FRAX and 4.87 for QFracture for hip fractures. Moreover, O/E raised as the risk increased for both tools and in almost all age groups. When using the recommended assessment thresholds, <6% and 10% of major osteoporotic and hip fractures would have been identified, respectively. In conclusion, FRAX and QFracture displayed acceptable discrimination, although both tools significantly underestimated the risk of fragility fractures in PWH. The recommended assessment thresholds may not be appropriate for this population as they were unable to identify individuals with fragility fractures during follow-up.

Lost in Translation: Evaluation of Subcutaneous Interferon-ß Treatment for SARS-CoV-2 Infection in Real Life.

Despite in vitro activity of interferon-ß (IFN-ß) against SARS-CoV-2 infection, its clinical efficacy remains controversial. We evaluated the impact of IFN-ß treatment in a cohort of 3590 patients hospitalized with COVID-19 during March−April 2020. The primary endpoint was a composed variable of admission to intensive care unit (ICU)/death. Overall, 153 patients (4%) received IFN-ß. They were significantly more severely ill, with a worse clinical and analytical situation, explaining a higher ICU admission (30% vs. 17%; p < 0.01), and a shorter time to the composed variable. In a Cox regression analysis, older age, lymphopenia, renal failure, or increased neutrophil-to-lymphocyte ratio were associated with a greater hazard ratio (HR) of admission at ICU/death. Notably, the HR of IFN-ß for the outcome variable was no longer significant after adjustment (HR, 1.03; 95% CI, 0.82−1.30), and different sensitivity analysis (early IFN use, ICU admission) showed no changes in the estimates. A propensity score matching analysis showed no association of IFN-ß therapy and outcome. In conclusion, in this large cohort of hospitalized COVID-19 patients, IFN-ß was used mainly in patients with advanced disease, reflecting an important bias of selection. After adjusting by severity, IFN-ß was not associated with a higher rate of ICU admission or mortality.

Shannon entropy as a reliable score to diagnose human fibroelastic degenerative mitral chords: A micro-ct ex-vivo study.

This paper is aimed at identifying by means of micro-CT the microstructural differences between normal and degenerative mitral marginal chordae tendineae. The control group is composed of 21 normal chords excised from 14 normal mitral valves from heart transplant recipients. The experimental group comprises 22 degenerative fibroelastic chords obtained at surgery from 11 pathological valves after mitral repair or replacement. In the control group the superficial endothelial cells and spongiosa layer remained intact, covering the wavy core collagen. In contrast, in the experimental group the collagen fibers were arranged as straightened thick bundles in a parallel configuration. 100 cross-sections were examined by micro-CT from each chord. Each image was randomized through the K-means machine learning algorithm and then, the global and local Shannon entropies were obtained. The optimum number of clusters, K, was estimated to maximize the differences between normal and degenerative chords in global and local Shannon entropy; the p-value after a nested ANOVA test was chosen as the parameter to be minimized. Optimum results were obtained with global Shannon entropy and 2≤K≤7, providing p < 0.01; for K=3, p = 2.86·10-3. These findings open the door to novel perioperative diagnostic methods in order to avoid or reduce postoperative mitral valve regurgitation recurrences.

Human Monkeypox in People With HIV: Transmission, Clinical Features, and Outcome.

We describe the first 25 persons with HIV diagnosed with human monkeypox virus (MPXV) in our hospital in an ongoing outbreak in Spain. Proctitis was the predominant finding in 52%, and MPXV DNA was detected in rectal swabs from 90%. Proctitis and demonstration of MPXV in rectal swabs support the sexual transmission of MPXV.

Mechanical Performance of Recycled Reinforced Polyamide from Rejected Railway Fastenings Flanged Plates.

The superstructure of modern railway lines uses tons of technical polymeric material spread along the track with mechanical, insulating and damping functions. Many of these parts are rejected because they do not pass the quality controls, generating a large accumulation of plastic waste of high economic value. Therefore, this study is aimed at determining the optimum degree of recyclability by mechanical crushing of geometrically defective (and so rejected) railway fastenings flanged plates injected with short fiberglass-reinforced polyamide. After recycling, the material must guarantee its physical and mechanical properties required to ensure the future in-service conditions of the highly responsible components that guarantee the maintenance of the railway gauge. Viscosity, mechanical properties (tensile test), Charpy and fracture toughness as well as fatigue performance were determined for ten successive recyclings. It has been found that the drop of viscosity is the most restrictive limitation, allowing three recyclings of the material. All the properties measured have experienced a noticeable reduction after 10 recyclings. Specifically, viscosity is reduced by 15%, ultimate strength by 70%, yield stress by 41% strain under maximum load lost by 70%, Young's modulus lost by 38%, Charpy impact strength by 70%, fatigue resistance by 69% and fracture toughness lost by 80%. With the development of this study and taking into account that the market price of the flanged plates is valued at approximately 8 k€/km, of which around 5 k€/km corresponds to the raw material, the recovery of this material not only represents a great environmental benefit but also an economic one.

HTLV-2 Enhances CD8+ T Cell-Mediated HIV-1 Inhibition and Reduces HIV-1 Integrated Proviral Load in People Living with HIV-1.

People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals.

Impact of SARS-CoV-2-specific memory B cells on the immune response after mRNA-based Comirnaty vaccine in seronegative health care workers.

Purpose: To analyze the impact of SARS-COV-2-specific memory B cells (MBC) on the immune response after two doses of mRNA-based Comirnaty COVID-19 vaccine in seronegative health care workers. This study is seeking a rationale for boosting vaccines. Methods: Longitudinal study including 31 seronegative health care workers with undetectable specific MBCs (IgG-MBC- group), 24 seronegative with detectable specific MBCs (IgG-MBC+ group), and 24 seropositive with detectable specific MBCs (IgG+MBC+ group). The level of antibodies that inhibit ACE2-RBD interaction, and anti-Spike IgG, IgA, and IgM antibodies was quantified by ELISA. In addition, specific memory B and T cells were quantified by flow cytometry. Results: The level of specific MBCs, and isotypes, in the IgG-MBC- group was lower compared to that found in IgG-MBC+ (p = 0.0001) and IgG+MBC+ (p < 0.0001) groups, respectively. ACE2-RBD neutralizing antibodies and anti-S IgG antibodies were at lower levels in the IgG-MBC-group after the vaccine. Specific MBCs directly correlated with specific CD4+ T cells (although not significant, p = 0.065), while no correlation was found with specific CD8+ T cells (p = 0.156) after the vaccine. In parallel, ACE2-RBD neutralizing antibodies only positively correlated with specific CD4+ T cells (p = 0.034). Conclusion: IgG-MBC- individuals showed the worst humoral and cellular responses, both in frequency and magnitude, after vaccination. Individuals whose antibodies wane and become undetectable after a given period of time post vaccination and show no specific MBCs are less protected and hence are good candidates for boosting vaccine. On the other hand, seronegative individuals with specific MBC showed faster and higher responses compared to the IgG-MBC- group.